In Vitro Drug Susceptibility Profile Of Leishmania Donovani Isolates Obtained From Primary And Relapse Visceral Leishmaniasis Patients With And Without Human Immunodeficiency Virus Co-infection Gondar Northwest Ethiopia

Background: Leishmania and HIV coinfection is a major public health problem in more than 35rncountries worldwide. The impaired immune function of VL/HIV-coinfected patients may: favorrnthe reactivation of latent Leishmania infection; induce a more severe presentation of VL; cause arnpoorer therapeutic response, and increase the risk of relapse after treatment. One of the majorrnchallenges in the management of VL/HIV coinfection is developing an effective drug therapyrnthat not only resolves the first episode of VL but also prevents relapse. This study aimed tornassess the in vitro drug susceptibility profile of clinical isolates of Leishmania in HIV positivernand negative patients obtained during the first VL episode before treatment and during VLrnrelapses on patients who attended LRTC of University of Gondar, Gondar, northwest Ethiopia,rnbetween January 1, 2020, and December 30, 2020. rnMethod: We evaluated the in vitro susceptibility to amphotericin B (AmB), paromomycinrn(PMM), and miltefosine (MLT) of 30 L. donovani isolates obtained from primary and relapse VLrnpatients with and without HIV co-infection. All 30 strains of L.donovani were tested at thernpromastigote stage whereas, 10 randomly selected strains of L.donovani were tested at thernamastigote stage to three antileishmanial drugs. rnResults: The median inhibitory concentration (ICrn) of AmB, PMM, and MLT againstrnpromastigotes was 0.221+0.108 µM, 13.49+6.92 µM, 3.77+1.77 µM respectively. Similarly, thernmedian inhibitory concentration (ICrn50rn50rn) of AmB, PMM, and MLT against amastigotes wasrn0.171+0.027µM, 10.80+ 4.12 µM, and 3.63+1.72 µM, respectively. In a comparison of medianrninhibitory concentration (ICrn) obtained against both stages of L.donovani strains collected fromrnprimary VL with both stages of L.donovani strains collected from relapse VL for all the threernreference antileishmanial drugs tested, the median inhibitory concentration (ICrn50rn) observedrnagainst strains from relapse VL was higher than the median inhibitory concentration (ICrn)rnobserved against strains from primary VL. The difference in the median inhibitory concentrationrn(ICrn) against strains from relapse VL with primary VL, was statistically significant( p = 0.03)rnfor AmB against amastigote stages, but not promastigote stage, whereas the difference in medianrninhibitory concentration (ICrn50rn) obtained for PMM and MLT against both stages of the parasitesrnwas not statistically significant. Likewise, strains from HIV coinfected VL patients withrnmultiple relapses showed an increase in ICrn50rn50rn50rn value for AmB and MLT in both parasite stages. rn50rnThe current study showed that in vitro susceptibility of strains decreased progressively inrnrelapsing patients compared with primary VL patients. rnConclusion: Thus, our findings suggest that AmB and MLT resistant parasites may indeedrnemerge in repeatedly treated relapse VL cases in HIV coinfected patients, warranting the needrnfor continuous close epidemiological monitoring of L. donovani susceptibility; and also, thernresults of such studies may reveal the need to re-examine the current therapy policies in HIVrncoinfected VL patients.

Get Full Work

Report copyright infringement or plagiarism